-Evaluation of women with hirsutism, virilization, and
oligo-amenorrhea

-Evaluation of women with symptoms or signs of possible
testosterone deficiency

-Evaluation of infants with ambiguous genitalia or
virilization

-Diagnosis of androgen-secreting tumors

Testosterone, Total and Bioavailable

-This is the recommended second-level test for suspected
increases or decreases in physiologically active testosterone

-Assessment of androgen status in cases with suspected or known
sex hormone-binding globulin binding abnormalities

-Assessment of functional circulating testosterone in early
pubertal boys and older men

-Assessment of functional circulating testosterone in women with
symptoms or signs of hyperandrogenism but normal total testosterone
levels

-Monitoring of testosterone therapy or antiandrogen therapy in
older men and in females

Profile Information

Test ID

Reporting Name

Available Separately

Always Performed

BATS

Testosterone, Bioavailable, S

No

Yes

TTST

Testosterone, Total, S

Yes

Yes

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Serum

Specimen Required

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 1 mL

Additional Information:
Patient's age and sex are required.

Specimen Minimum Volume

0.6 mL

Specimen Stability Information

Specimen Type

Temperature

Time

Serum

Refrigerated (preferred)

14 days

Frozen

60 days

Reference Values

TESTOSTERONE, TOTAL

Males

0-5 months: 75-400 ng/dL

6 months-9 years: <7-20 ng/dL

10-11 years: <7-130 ng/dL

12-13 years: <7-800 ng/dL

14 years: <7-1,200 ng/dL

15-16 years: 100-1,200 ng/dL

17-18 years: 300-1,200 ng/dL

≥19 years: 240-950 ng/dL

Tanner Stages*

I (prepubertal): <7-20

II: 8-66

III: 26-800

IV: 85-1,200

V (young adult): 300-950

Females

0-5 months: 20-80 ng/dL

6 months-9 years: <7-20 ng/dL

10-11 years: <7-44 ng/dL

12-16 years: <7-75 ng/dL

17-18 years: 20-75 ng/dL

≥19 years: 8-60 ng/dL

Tanner Stages*

I (prepubertal): <7-20

II: <7-47

III: 17-75

IV: 20-75

V (young adult): 12-60

*Puberty onset (transition from Tanner stage I to Tanner stage
II) occurs for boys at a median age of 11.5 (±2) years and
for girls at a median age of 10.5 (±2) years. There is
evidence that it may occur up to 1 year earlier in obese girls and
in African American girls. For boys, there is no definite proven
relationship between puberty onset and body weight or ethnic
origin. Progression through Tanner stages is variable. Tanner stage
V (young adult) should be reached by age 18.

TESTOSTERONE, BIOAVAILABLE

Males

≤19 years: not established

20-29 years: 83-257 ng/dL

30-39 years: 72-235 ng/dL

40-49 years: 61-213 ng/dL

50-59 years: 50-190 ng/dL

60-69 years: 40-168 ng/dL

≥70 years: not established

Females (non-oophorectomized)

≤19 years: not established

20-50 years (on oral estrogen): 0.8-4.0 ng/dL

20-50 years (not on oral estrogen): 0.8-10 ng/dL

>50 years: not established

Day(s) and Time(s) Performed

Monday through Friday

Test Classification

This test was developed and its performance characteristics
determined by Mayo Clinic in a manner consistent with CLIA
requirements. This test has not been cleared or approved by the
U.S. Food and Drug Administration.

CPT Code Information

84403-Testosterone, total

84410-Testosterone, bioavailable

LOINC Code Information

Test ID

Test Order Name

Order LOINC Value

TTBS

Testosterone, Total and Bioavail,
S

In Process

Result ID

Test Result Name

Result LOINC Value

82978

Testosterone, Bioavailable,
S

2990-0

8533

Testosterone, Total, S

2986-8

Clinical Information

Testosterone is the major androgenic hormone. It is responsible
for the development of the male external genitalia and secondary
sexual characteristics. In females, its main role is as an estrogen
precursor. In both genders, it also exerts anabolic effects and
influences behavior.

In men, testosterone is secreted by the testicular Leydig cells
and, to a minor extent, by the adrenal cortex. In premenopausal
women, the ovaries are the main source of testosterone, with minor
contributions by the adrenals and peripheral tissues. After
menopause, ovarian testosterone production is significantly
diminished. Testosterone production in testes and ovaries is
regulated via pituitary-gonadal feedback involving lutenizing
hormone (LH), and to a lesser degree, inhibins and activins.

Most circulating testosterone is bound to sex hormone-binding
globulin (SHBG), which in men also is called testosterone-binding
globulin. A lesser fraction is albumin bound and a small proportion
exists as free hormone. Historically, only the free testosterone
was thought to be the biologically active component. However,
testosterone is weakly bound to serum albumin and dissociates
freely in the capillary bed, thereby becoming readily available for
tissue uptake. All non-SHBG bound testosterone is therefore
considered bioavailable.

During childhood, excessive production of testosterone induces
premature puberty in boys and masculinization in girls. In adult
women, excess testosterone production results in varying degrees of
virilization, including hirsutism, acne, oligo-amenorrhea, or
infertility. Mild-to-moderate testosterone elevations are usually
asymptomatic in males, but can cause distressing symptoms in
females. The exact causes for mild-to-moderate elevations in
testosterone often remain obscure. Common causes of pronounced
elevations of testosterone include genetic conditions (eg,
congenital adrenal hyperplasia), adrenal, testicular, and ovarian
tumors, and abuse of testosterone or gonadotrophins by
athletes.

Decreased testosterone in females causes subtle symptoms. These
may include some decline in libido and nonspecific mood changes. In
males, it results in partial or complete degrees of hypogonadism.
This is characterized by changes in male secondary sexual
characteristics and reproductive function. The cause is either
primary or secondary/tertiary (pituitary/hypothalamic) testicular
failure. In adult men, there also is a gradual modest but
progressive decline in testosterone production starting between the
fourth and sixth decade of life. Since this is associated with a
simultaneous increase of SHBG levels, bioavailable testosterone may
decline more significantly than apparent total testosterone,
causing nonspecific symptoms similar to those observed in
testosterone deficient females. However, severe hypogonadism
consequent to aging alone is rare.

Measurement of total testosterone (TTST / Testosterone, Total,
Serum) is often sufficient for diagnosis, particularly if it is
combined with measurements of LH (LH / Luteinizing Hormone [LH],
Serum) and follicle stimulating hormone (FSH) (FSH /
Follicle-Stimulating Hormone [FSH], Serum). However, these tests
may be insufficient for diagnosis of mild abnormalities of
testosterone homeostasis, particular if abnormalities in SHBG (SHBG
/ Sex Hormone Binding Globulin [SHBG], Serum) function or levels
are present. Additional measurements of bioavailable (TTBS /
Testosterone, Total and Bioavailable, Serum) or free testosterone
(TGRP / Testosterone, Total and Free, Serum) are recommended
in this situation. While both bioavailable and free testosterone
can be used for the same indications, determination of bioavailable
testosterone levels may be superior to free testosterone
measurement in most situations.

Interpretation

Total Testosterone and general interpretation of
testosterone abnormalities:

In males:

Decreased testosterone levels indicate partial or complete
hypogonadism. In hypogonadism, serum testosterone levels are
usually below the reference range. The cause is either primary or
secondary/tertiary (pituitary/hypothalamic) testicular failure.

In prepubertal boys, increased levels of testosterone are seen
in precocious puberty. Further work-up is necessary to determine
the cause(s) of precocious puberty.

In adult men, testicular or adrenal tumors or androgen abuse
might be suspected if testosterone levels exceed the upper limit of
the normal range by more than 50%.

Monitoring of testosterone replacement therapy:

Aim of treatment is normalization of serum testosterone and LH.
During treatment with depot-testosterone preparations, trough
levels of serum testosterone should still be within the normal
range, while peak levels should not be significantly above the
normal young adult range.

Monitoring of antiandrogen therapy:

Aim is usually to suppress testosterone levels to castrate
levels or below (no more than 25% of the lower reference range
value).

In females:

Decreased testosterone levels may be observed in primary or
secondary ovarian failure, analogous to the situation in men,
alongside the more prominent changes in female hormone levels. Most
women with oophorectomy have a significant decrease in testosterone
levels.

Increased testosterone levels may be seen in:

-Congenital adrenal hyperplasia. Nonclassical (mild) variants
may not present in childhood, but during or after puberty. In
addition to testosterone, multiple other androgens or androgen
precursors, such as 17 OH-progesterone (OHPG /
17-Hydroxyprogesterone, Serum), are elevated, often to a greater
degree than testosterone.

-Analogous to males, but at lower levels in prepubertal girls,
increased levels of testosterone are seen in precocious
puberty.

-Ovarian or adrenal neoplasms. High estrogen values also may be
observed and LH and FSH are low or "normal." Testosterone-producing
ovarian or adrenal neoplasms often produce total testosterone
values >200 ng/dL.

The efficacy of testosterone replacement in females is under
study. If it is used, then levels should be kept within the normal
female range at all times. Bioavailable (TTBS / Testosterone, Total
and Bioavailable, Serum) or free testosterone (TGRP / Testosterone,
Total and Free, Serum) levels should also be monitored to avoid
overtreatment.

Monitoring of antiandrogen therapy:

Antiandrogen therapy is most commonly employed in the management
of mild-to-moderate idiopathic female hyperandrogenism, as seen in
polycystic ovarian syndrome. Total testosterone levels are a
relatively crude guideline for therapy and can be misleading.
Therefore, bioavailable (TTBS/80065 Testosterone, Total and
Bioavailable, Serum) or free testosterone (TGRP/8508 Testosterone,
Total and Free, Serum) also should be monitored to ensure treatment
adequacy. However, there are no universally agreed biochemical end
points and the primary treatment end point is the clinical
response.

Testosterone, Total and Bioavailable:

Usually, bioavailable (and free testosterone) levels parallel
the total testosterone levels. However, a number of conditions and
medications are known to increase or decrease the sex
hormone-binding globulin (SHBG) concentration, which may cause
total testosterone concentration to change without necessarily
influencing the bioavailable or free testosterone concentration, or
vice versa:

-Treatment with corticosteroids and sex steroids (particularly
oral conjugated estrogen) can result in changes in SHBG levels and
availability of sex-steroid binding sites on SHBG. This may make
diagnosis of subtle testosterone abnormalities difficult.

-Inherited abnormalities in SHBG binding.

-Liver disease and severe systemic illness.

-In pubertal boys and adult men, mild decreases of total
testosterone without LH abnormalities can be associated with
delayed puberty or mild hypogonadism. In this case, either
bioavailable or free testosterone measurements are better
indicators of mild hypogonadism than determination of total
testosterone levels.

-In polycystic ovarian syndrome and related conditions, there is
often significant insulin resistance, which is associated with low
SHBG levels.

-Consequently, bioavailable or free testosterone levels may be
more significantly elevated.

Either bioavailable (TTBS / Testosterone, Total and
Bioavailable, Serum) or free testosterone (TGRP / Testosterone,
Total and Free, Serum) should be used as supplemental tests to
total testosterone in the above situations. The correlation
coefficient between bioavailable and free testosterone (by
equilibrium dialysis) is 0.9606. However, bioavailable testosterone
is usually the preferred test, as it more closely reflects total
bioactive testosterone, particularly in older men. These men not
only have elevated SHBG levels, but albumin levels may also vary,
due to coexisting illnesses.